Journal Article

Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity

Penelope D. Sanchez-Gonzalez, Francisco J. Lopez-Hernandez, Fernando Perez-Barriocanal, Ana I. Morales and Jose M. Lopez-Novoa

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 11, pages 3484-3495
Published in print November 2011 | ISSN: 0931-0509
Published online May 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr195
Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity

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Background. Nephrotoxicity is the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Our aim was to investigate the protective effect of quercetin on cisplatin nephrotoxicity in a rat tumour model in vivo and to examine the mechanisms of renal protection.

Methods. Breast adenocarcinoma (13762 Mat B-III) cells were inoculated subcutaneously in male Fischer rats and 7 days later, the rats were administered daily with quercetin [50 mg/kg/day, intraperitoneally (i.p.)] or vehicle. Four days after that, the rats were given a single dose of cisplatin (4 mg/kg, i.p.) or vehicle. Tumour growth and renal function were monitored throughout the experiment. Two or 6 days after cisplatin administration, the rats were killed and the kidneys and tumours were removed to examine renal function and toxicity markers in both tissues.

Results. In the kidney, cisplatin treatment induced: (i) a decrease in renal blood flow and glomerular filtration rate, (ii) tubular necrosis/apoptosis, (iii) increased lipid peroxidation and decreased endogenous antioxidant systems, (iv) increased expression of inflammation markers and (v) increased activity of the apoptosis executioner caspase-3. Cisplatin effectively reduced tumour size and weight.

Conclusions. Co-treatment with quercetin partially prevented all the renal effects of cisplatin, whereas it did not impair its anti-tumour activity. In conclusion, in a model of tumour-bearing rats, quercetin prevents the nephrotoxic effect of cisplatin without affecting its anti-tumour activity.

Keywords: acute kidney injury; cisplatin; nephrotoxicity; quercetin; renoprotection

Journal Article.  6097 words.  Illustrated.

Subjects: Nephrology

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